Scribd
Upload
25 views3 pages

Regulation of Glycolysis

Uploaded by

x7pc5jrdjd
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
Download as ODT, PDF, TXT or read online on Scribd
25 views3 pages

Regulation of Glycolysis

Uploaded by

x7pc5jrdjd
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
Download as ODT, PDF, TXT or read online on Scribd
You are on page 1/ 3

Regulation of glycolysis

Introduction

Glycolysis derived from the Greek term glyk-, "sweet," and the word lysis, means
"solubilization"

 Glycolysis essentially means glucose + lysis i.e breakdown of glucose


 This is one of the most ancient pathway known to human kind
 There are a series of biochemical reactions through which 1 molecule of glucose is
metabolized to yield 2 moles of pyruvate (pyruvic acid) and 2 ATP as net energy

As we know in glycolytic pathways, there are certain irreversible enzyme catalyzed reactions
they have negative ΔG. These can be potential regulatory sites of the pathway

 The preliminary function of glycolysis is to produce energy (ATP), it must be regulated so that
energy is released(ATP is generated) under needful situations

 In glycolysis, the reactions catalyzed by hexokinase (glucokinase), phosphofructokinase, and


pyruvate kinase are such irreversible reactions and can behave as checkpoints for regulation of
the entire pathway

 These enzymes regulated by

1.Availability of substrate

2.Concentration ofenzymes responsible for rat-limiting step

3.Allosteric regulation of enzymes regulates pathway with in


Milliseconds

4.Covalent modification of enzymes (e.g. phosphorylation) regulates


pathway within few seconds

5.Transcriptionalcontrol(hours)

 The intracellular concentration as well as transcription of all three enzymes is well regulated
by hormonal action.

 Hormone pair of insulin-glucagon secreted by pancreas in response to sudden rise and fall in
blood glucose levels. Insulin is also released in response to sudden rise in amino acid levels in
the blood. As a universal effect insulin promotes the storage of excessive energy under fed state
while glucagon acts antagonist to insulin in every manner.

Page 1
 Insulin promotes the transcription of glucokinase (hexokinase), phosphofructokinase, and
pyruvate kinase, while glucagon demotes the transcription of these 3 enzymes
The visible effects can be seen when an individual is well-fed or is continually starved.

Checkpoint 1: Regulation of Hexokinase/glucokinase

 Hexokinase enzyme initiates glycolysis in muscles, brain it has high affinity for glucose so
even at suboptimal glucose levels in blood the enzyme favors glycolysis

 The end product of this reaction glucose-6-phosphate though acts as a feedback inhibitor the
overall reaction helps expenditure of too much of cellullar ATP when glucose is abundant

 Whereas the counterpart of hexokinase enzyme in liver and pancreas is glucokinase, acts at a
higher concentration of glucose

 Thus when glucose concentration is at peak after rich carbohydrate intake the enzyme helps
liver to remove excess glucose and thereby regulate blood glucose after meals. Moreover the
enzyme activity is not inhibited by glucose-6-phosphate

Checkpoint 2: Regulation of Phosphofructokinase

 Phosphofructokinase (PFK) catalyses the phosphorylation and converting fructose-6-


phosphate to fructose-1-6-bisphosphate an irreversible as well as rate limiting reaction of
glycolytic pathway

 Phosphofructokinase is a tetramer having four identical subunits. ATP is allosteric inhibitor of


PFK hence glycolysis is down regulated when intracellular ATP level is high

 The allosteric mechanism includes binding of ATP at a distinct site on PFK different from
catalytic site and inducing a conformational change that rotates positions of two amino acids
Glu161 and Arg162

 When low affinity for substrate is observed the charges are imbalanced as phosphate on F6P is
repeled by Glu161

While under high affinity for substrate F6P results in stabilization of charges between phosphate
at 6th position and arginine at 162nd position

 This conformationl change helps maintain intracellular ionic strength and regulate blood pH
further reducing glycolysis and preventing accumulation of acids due to rigorous muscular
activity under low
oxygen environment. It also helps regulate and minimize lactoacidosis

Page 2
 Other regulators of this enzyme are ATP(feedback inhibition),AMP(reverse inhibition),
ADP(allosteric inhibition), citrate(feedback inhibition) and β-D-fructose 2-6-bisphosphate (feed-
forward inhibition

Checkpoint 3: Regulation of pyruvate kinase

 This is the last enzyme catalyzed reaction of glycolysis that is irreversible and can regulate
entire pathway

 At low glucose concentration covalent phosphorylation inhibits the pyruvate kinase activity

 But if fructose 1,6 bisphosphate is formed, the reaction is activated instead and as a feed
forward activator fructose-1,6-bisphosphate leads the enzyme catalysed reaction in forward
direction

 Other regulators are AMP and ADP that positively regulate the reaction while ATP is a
negative effector of the reaction

MLS 2024

Page 3

You might also like